Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning.
Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning.
复制标题
DOI：
10.1371/journal.pmed.0040105
复制
发表时间：
2007-04
期刊：
影响因子：
15.8
通讯作者：
Majeed, Azeem
中科院分区：
文献类型：
--
作者：
Morgan, Oliver W.;Griffiths, Clare;Majeed, Azeem
扑热息痛（对乙酰氨基酚）中毒是英国和美国急性肝衰竭的主要原因。需要采取成功的干预措施来减少扑热息痛中毒造成的危害。为了实现这一目标，英国政府于 1998 年颁布立法，限制商店出售的扑热息痛的包装尺寸。几项研究报告最近涉及扑热息痛的致命中毒事件有所减少。我们使用间断时间序列分析来评估最近扑热息痛死亡人数的下降是否与涉及阿司匹林、扑热息痛化合物、抗抑郁药或非药物中毒自杀的致命中毒趋势不同。我们直接计算了 1993 年至 2004 年英格兰和威尔士扑热息痛中毒的年龄标准化死亡率。我们使用普通最小二乘回归模型，在 1999 年分为干预前和干预后部分。该模型包括时间序列内的自相关项。我们测试了干预前后段之间水平和斜率的变化。为了评估观察到的时间序列变化是否是扑热息痛所特有的，我们与涉及复合扑热息痛（法规未涵盖）、阿司匹林、抗抑郁药和非中毒自杀死亡的中毒死亡进行了比较。我们通过计算每个比较系列与扑热息痛的比率并对比率应用分段回归模型来进行此比较。比率水平或斜率没有变化表明与对照系列相比没有差异。大约有 2,200 人因扑热息痛而死亡。年龄标准化死亡率从1993年的每百万人8.1人上升到1997年的每百万人8.8人，随后下降到2004年的每百万人5.3人左右。法规出台后，死亡人数下降了每百万人2.69人（p = 0.003）。扑热息痛化合物、阿司匹林和抗抑郁药的年龄标准化死亡率趋势与扑热息痛大致相似，直到 1997 年一直在上升，然后下降。研究期间非药物中毒自杀率也有所下降，但在 1993 年最高。分段回归模型显示，复合扑热息痛的年龄标准化死亡率在法规出台后下降较少（p = 0.012），但随后下降得更快（p = 0.031）。然而，在法规出台后，阿司匹林和抗抑郁药的年龄标准化价格下降幅度与扑热息痛类似。法规出台后，非药物中毒自杀率下降的速度与扑热息痛类似。限制扑热息痛供应的法规的出台与扑热息痛中毒死亡率的下降同时发生。然而，涉及阿司匹林、抗抑郁药以及较小程度的扑热息痛化合物的致命中毒也表现出类似的趋势。这就提出了一个问题：扑热息痛死亡人数的下降是由于法规所致，还是药物中毒死亡率下降的更广泛趋势的一部分。我们发现几乎没有证据支持这一假设，即 1998 年限制包装尺寸的法规导致与其他药物或非药物中毒自杀相比，涉及扑热息痛的中毒死亡人数减少得更多。对英格兰和威尔士扑热息痛中毒死亡率的分析并不支持限制包装尺寸的法规导致死亡人数减少的观点。扑热息痛（在美国被称为对乙酰氨基酚）是一种廉价而有效的止痛药。它被广泛用于缓解轻微疼痛以及发烧和头痛。扑热息痛的推荐剂量被认为对人类是安全的，但过量服用是有毒的，可能导致肝衰竭和死亡。由于这种药物很容易获得，因此每年都会发生许多意外或故意过量服用的情况。在英国，扑热息痛中毒是急性肝衰竭的最常见原因。 1998 年底，英国出台了新法律，试图减少扑热息痛过量服用的数量。这些法律规定，药店不得销售含有超过 32 片的扑热息痛包装，其他商店也不得销售含有超过 16 片的包装。出台这项法律的原因之一是，许多自杀事件都没有预先计划，因此，如果人们更难获得或保留大量药片，他们尝试自杀或意外服药过量的可能性就较小。这些新法律出台后，英国因扑热息痛过量导致的死亡人数下降。然而，死亡人数下降的原因可能有多种，而不仅仅是关于扑热息痛包装尺寸的新法律的结果。例如，由于社会的其他变化，自杀率可能一直在下降，而扑热息痛死亡率的下降可能只是这一趋势的一部分。重要的是要查明为解决公共卫生问题而引入的法律变更是否确实带来了更好的变化。这些知识也与正在考虑类似变革的其他国家相关。研究人员使用了国家统计局的数据，该办公室掌握着英格兰和威尔士药物中毒死亡的信息。然后，这些数据按照死亡证明上提到的药物类型进行细分。研究人员比较了以下药物的死亡率：扑热息痛；含扑热息痛的化合物（不受新包装尺寸法的约束）；阿司匹林;抗抑郁药；最后是非药物中毒自杀。将扑热息痛死亡率与其他药物或非药物自杀死亡率进行比较的原因是，这种方法可以让研究人员了解扑热息痛死亡率的下降是否遵循中毒或自杀率的总体趋势。如果新法律出台后扑热息痛死亡率下降，但其他类型的中毒或自杀率没有下降，那么新法律与扑热息痛自杀率下降之间就会存在联系。研究人员比较了 1998 年底之前（当时出台了关于扑热息痛包装尺寸的新法律）和之后特定时间段内的死亡数据。总体而言，1993年至2004年间，有近2,200人因扑热息痛而死亡。与1998年底前后相比，每年因扑热息痛而死亡的人数大幅下降。然而，在此期间，每年涉及任何药物的死亡人数以及非药物自杀人数也有所下降。在将扑热息痛死亡趋势与其他中毒或自杀死亡趋势进行比较时，研究人员没有发现任何统计证据表明扑热息痛死亡人数的下降与中毒或自杀死亡率的总体趋势有任何不同。尽管扑热息痛死亡率在新的包装尺寸法规出台后立即下降，但这项研究表明这种联系可能只是巧合。研究人员找不到任何数据支持新法律导致扑热息痛死亡人数下降的观点。然而，这是一项观察性研究，而不是真正的实验性研究：研究人员显然无法建立同等的“实验”组和“对照组”进行比较。很难最终证明或反驳此类新法律是否有效。请通过此摘要的在线版本访问这些网站：http://dx.doi.org/10.1371/journal.pmed.0040105 可从 Medline Plus 获取有关自杀的信息 维基百科有关于扑热息痛的条目（请注意，维基百科是任何人都可以编辑的互联网百科全书） 有关英国药物监管的信息可从药品和医疗保健监管机构获取。国家统计局提供有关自杀的关键经济和社会数据。英国，并参与了许多其他重要项目
Paracetamol (acetaminophen) poisoning is the leading cause of acute liver failure in Great Britain and the United States. Successful interventions to reduced harm from paracetamol poisoning are needed. To achieve this, the government of the United Kingdom introduced legislation in 1998 limiting the pack size of paracetamol sold in shops. Several studies have reported recent decreases in fatal poisonings involving paracetamol. We use interrupted time-series analysis to evaluate whether the recent fall in the number of paracetamol deaths is different to trends in fatal poisoning involving aspirin, paracetamol compounds, antidepressants, or nondrug poisoning suicide. We calculated directly age-standardised mortality rates for paracetamol poisoning in England and Wales from 1993 to 2004. We used an ordinary least-squares regression model divided into pre- and postintervention segments at 1999. The model included a term for autocorrelation within the time series. We tested for changes in the level and slope between the pre- and postintervention segments. To assess whether observed changes in the time series were unique to paracetamol, we compared against poisoning deaths involving compound paracetamol (not covered by the regulations), aspirin, antidepressants, and nonpoisoning suicide deaths. We did this comparison by calculating a ratio of each comparison series with paracetamol and applying a segmented regression model to the ratios. No change in the ratio level or slope indicated no difference compared to the control series. There were about 2,200 deaths involving paracetamol. The age-standardised mortality rate rose from 8.1 per million in 1993 to 8.8 per million in 1997, subsequently falling to about 5.3 per million in 2004. After the regulations were introduced, deaths dropped by 2.69 per million (p = 0.003). Trends in the age-standardised mortality rate for paracetamol compounds, aspirin, and antidepressants were broadly similar to paracetamol, increasing until 1997 and then declining. Nondrug poisoning suicide also declined during the study period, but was highest in 1993. The segmented regression models showed that the age-standardised mortality rate for compound paracetamol dropped less after the regulations (p = 0.012) but declined more rapidly afterward (p = 0.031). However, age-standardised rates for aspirin and antidepressants fell in a similar way to paracetamol after the regulations. Nondrug poisoning suicide declined at a similar rate to paracetamol after the regulations were introduced. Introduction of regulations to limit availability of paracetamol coincided with a decrease in paracetamol-poisoning mortality. However, fatal poisoning involving aspirin, antidepressants, and to a lesser degree, paracetamol compounds, also showed similar trends. This raises the question whether the decline in paracetamol deaths was due to the regulations or was part of a wider trend in decreasing drug-poisoning mortality. We found little evidence to support the hypothesis that the 1998 regulations limiting pack size resulted in a greater reduction in poisoning deaths involving paracetamol than occurred for other drugs or nondrug poisoning suicide. Analysis of mortality rates for paracetamol poisoning in England and Wales does not support the view that regulations limiting pack size have been responsible for a reduction in deaths. Paracetamol—known as acetaminophen in the United States—is a cheap and effective painkiller. It is widely used to relieve minor aches and pains as well as fevers and headaches. Recommended doses of paracetamol are considered safe in humans, but overdoses are toxic and can cause liver failure and death. Because this drug is very easy to get hold of, there are many overdoses each year, either accidental or deliberate. In the UK, paracetamol poisoning is the most common cause of acute liver failure. Toward the end of 1998, new laws were introduced in the UK to try to reduce the number of paracetamol overdoses. These laws said that pharmacies could not sell packs of paracetamol containing more than 32 tablets and other shops could not sell packs with more than 16 tablets. One of the reasons behind the introduction of this law was that many suicides are not preplanned and, therefore, if it was harder for people to get hold of or keep large quantities of tablets, they might be less likely to attempt suicide or accidentally overdose. Following the introduction of these new laws, the number of deaths caused by paracetamol overdose in the UK dropped. However, it is possible that the drop in deaths came about for a variety of different reasons and not just as a result of the new laws on paracetamol pack size. For example, the suicide rate might have been falling anyway due to other changes in society and the fall in death rate from paracetamol might just have been part of that trend. It is important to find out whether the legal changes that were introduced to address a public health problem did in fact bring about a change for the better. This knowledge would also be relevant to other countries that are considering similar changes. The researchers used data from the Office of National Statistics, which holds information on drug poisoning deaths in England and Wales. These data were then broken down by the type of drug that was mentioned on the death certificate. The researchers compared death rates involving the following drugs: paracetamol; paracetamol-containing compounds (which were not subject to the new pack size laws); aspirin; antidepressant drugs; and then finally non-drug poisoning suicides. The reason for comparing death rates involving paracetamol against death rates involving other drugs, or non-drug suicide, was that this method would allow the researchers to see if the drop in paracetamol deaths followed overall trends in the poisoning or suicide rates or not. If the paracetamol death rate dropped following introduction of the new laws but the rates of other types of poisoning or suicide did not, then there would be a link between the new laws and a fall in paracetamol suicides. The researchers compared these death data within specific time periods before the end of 1998 (when the new laws on paracetamol pack size were introduced) and after. Overall, there were nearly 2,200 deaths involving paracetamol between 1993 and 2004. The number of deaths per year involving paracetamol dropped substantially when comparing the periods of time before the end of 1998 and after it. However, the number of deaths per year involving any drug, and the non-drug suicides, also fell during this period of time. When comparing the trends for paracetamol deaths with other poisoning or suicide deaths, the researchers did not find any statistical evidence that the fall in paracetamol deaths was any different to the overall trend in poisoning or suicide death rates. Although the paracetamol death rate fell immediately following the new laws on pack size, this study suggests the link might just be coincidence. The researchers could not find any data supporting the idea that the new laws caused a drop in paracetamol deaths. However, this was an observational study, not a true experimental one: the researchers here were clearly not able to set up equivalent “experimental” and “control” groups for comparison. It is very difficult to prove or disprove conclusively that new laws such as this are, or are not, effective. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040105 Information is available from Medline Plus about suicide Wikipedia has an entry on paracetamol (note that Wikipedia is an internet encyclopedia anyone can edit) Information about regulation of drugs in the UK is available from the Medicines and Healthcare Regulatory Agency The Office for National Statistics provides key economic and social data about the UK, and is involved in many other important projects